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National Institute of Environmental Health Sciences

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Publication Detail

Title: Intact microtubules are necessary for complete processing, storage and regulated secretion of von Willebrand factor by endothelial cells.

Authors: Sinha, S; Wagner, D D

Published In Eur J Cell Biol, (1987 Jun)

Abstract: The importance of intact microtubules in the processing, storage and regulated secretion of von Willebrand factor (vWf) from Weibel-Palade bodies in endothelial cells was investigated. Human umbilical vein endothelial cells treated for 1 h with colchicine (10(-6) M) or nocodozole (10(-6) M) lost their organized microtubular network. Stimulation of these cells with secretagogues (A23187, thrombin) produced only 30% release of vWf in comparison to control cells containing intact microtubules. The nocodazole treatment was reversible. One-hour incubation in the absence of the drug was sufficient for microtubules to reform and restore the full capacity of the cells to release vWf. Long-term incubation (24 h) of endothelial cells with microtubule-destabilizing agents had a profound effect on vWf distribution. In control cells, vWf was localized to organelles in the perinuclear region (i.e., endoplasmic reticulum and Golgi apparatus) and to Weibel-Palade bodies. In drug-treated cells vWf staining was dispersed throughout the cytoplasm, and Weibel-Palade bodies were absent. The vWf synthesized in the absence of microtubules contained significantly less large multimers than that produced by control cells. Since Weibel-Palade bodies specifically contain the large multimers, we hypothesize that the structural defect in vWf secreted by cells in the absence of microtubules is due to the lack of Weibel-Palade bodies in these cultures.

PubMed ID: 3305020 Exiting the NIEHS site

MeSH Terms: Benzimidazoles/pharmacology; Cells, Cultured; Colchicine/pharmacology; Endothelium/metabolism*; Female; Fluorescent Antibody Technique; Humans; Lumicolchicines/pharmacology; Microtubules/drug effects; Microtubules/metabolism*; Microtubules/ultrastructure; Nocodazole; Tubulin/analysis; Umbilical Veins; von Willebrand Factor/genetics; von Willebrand Factor/metabolism*

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